Corrigendum to “Proof-of-concept of a novel methylated PET tracer designed to enhance the Photostability of PM-PBB3” (Results in Chemistry, (2026), 20, C, (102979), (S2211715625009634), 10.1016/j.rechem.2025.102979)

The authors regret that, in the original article, Figure 2 has been published incorrectly. Figure 2 illustrated the evaluation of the binding of our newly developed compound to tau aggregates using fluorescent staining of brain sections. In the published article, the brain sections were described as being derived from human Alzheimer's disease (AD) brain tissue. However, the staining experiment shown in this figure was performed using brain sections from the rTg4510 tauopathy mouse model, and the figure corresponds to these data. We have therefore corrected the figure caption.(Figure presented) Figure 2 Photomicrographs of fluorescence staining with PM-PBB3 and Me-PM-PBB3 in rTg4510 mouse brain sections. Furthermore, corrections to the descriptions in the abstract and main text related to this figure. Corrigendum to the abstract Molecular imaging of tau protein accumulation plays a vital role in elucidating the pathology and enabling early diagnosis of tauopathies, including Alzheimer's disease (AD). [¹⁸F]PM-PBB3 is a promising tau positron emission computed tomography (PET) tracer with high selectivity and affinity for tau lesions in both AD and non-AD tauopathies. However, its clinical application is hindered by poor photostability owing to rapid photoisomerization. In this study, we synthesized a novel derivative of PM-PBB3, Me-PM-PBB3, by introducing a methyl group at the γ-position of the former to improve photostability. Compared to PM-PBB3, Me-PM-PBB3 showed a blue-shifted absorption maximum and lower molar extinction coefficient, resulting in a more than 100-fold increase in resistance to photodegradation. Fluorescence staining of the brain sections in rTg4510 mice, a tauopathy model, demonstrated that Me-PM-PBB3 bound to neurofibrillary tangles. PET imaging using rTg4510 mice revealed that [¹⁸F]Me-PM-PBB3 accumulates in the cortex and hippocampus, indicating its effectiveness as a tau PET tracer. However, increased non-specific binding in white matter was also observed, suggesting that structural modifications may affect its in vivo kinetics. Overall, this study presents a novel chemical approach to enhance the photostability of tau PET tracers, and the proof-of-concept was completed using Me-PM-PBB3. Corrigendum to the results and discussion (Fluorescent staining) The binding affinity of Me-PM-PBB3 for tau aggregates was evaluated using brain sections from rTg4510 mice, a tauopathy model. In line with previous findings, PM-PBB3 selectively bound to NFTs and dystrophic neurites, enabling the clear identification of tau pathology (Figure 2A). Similarly, Me-PM-PBB3 successfully bound to NFTs and dystrophic neurites, with a distinct tau pathology observed in the cerebral cortex (Figure 2B). These results suggest that the introduction of a bulky substituent into the conjugated diene structure does not substantially impair the ability of PM-PBB3 to bind tau aggregates. The lower fluorescence intensity of Me-PM-PBB3 than that of PM-PBB3 was primarily due to a significant decrease in its molar extinction coefficient relative to that of PM-PBB3. (Biological assessment) Next, we performed PET imaging in vivo using rTg4510 mice to evaluate brain uptake following intravenous injection of the ¹⁸F-labeled compounds. The PET images were used to calculate the standardized uptake value ratio (SUVR) as a quantitative index, referencing the cerebellar region with no tau accumulation [12]. The relative changes from the initial phase (C_t/C_{3 min}) were calculated by dividing the SUVR at each time point by that at 3 minutes post-injection, thereby excluding blood flow-affected radioactivity immediately after injection. In rTg4510 mice, [¹⁸F]PM-PBB3 exhibited prominent retention in the cerebral cortex and hippocampus, areas known to accumulate abundant NFTs. In contrast, littermate control mice (tTA mice) without tau pathology showed negligible signals in the same regions, consistent with the pathological specificity of the tracer (Figure 5A). [¹⁸F]Me-PM-PBB3 displayed a similar distribution pattern, with substantial uptake in the cortical and hippocampal regions of rTg4510 mice and minimal retention in tTA mice, indicating a comparable in vivo binding profile to that of [¹⁸F]PM-PBB3 (Figure 5B). Corrigendum to the conclusion In this study, we demonstrated that the introduction of a methyl group at the γ-position of the conjugated diene moiety in PM-PBB3 markedly enhances its photostability while preserving its binding affinity to tau aggregates. The newly developed derivative, Me-PM-PBB3, exhibited a ˃100-fold improvement in photostability compared to PM-PBB3. In vitro fluorescence staining of rTg4510 mouse brain sections and autoradiography using human AD brain sections confirmed binding to NFTs, and in vivo PET imaging using rTg4510 mice validated its accumulation in tau-rich brain regions, supporting its potential as a tau-imaging agent. This study provides a novel compound design strategy for radiotracers bearing conjugated alkene structures, which are widely used in Aβ and tau imaging. These findings indicate that the proof-of-concept has been completed, paving the way for the development of more stable radioligands. However, our findings also revealed that such structural modifications may inadvertently increase off-target binding, likely due to increased lipophilicity and reduced conformational linearity. Although the introduction of a methyl group at the γ-position of PM-PBB3 resulted in decreased specificity, it is conceivable that applying a similar approach to other PET tracers, or exploring different positions for substituent introduction, could lead to the development of compounds with improved photostability while maintaining high specific binding. Therefore, future efforts should focus on optimizing the balance between enhanced photostability and reduced off-target binding with the goal of developing radiotracers that achieve both high specificity and favorable pharmacokinetic profiles. These corrections do not affect the experimental results or the conclusion of the study. The authors would like to apologize for any inconvenience caused.